Pharmacy

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Image from Wikipedia

The US Food and Drug Administration (FDA) has expanded the approved use of vemurafenib (Zelboraf) to include the treatment of adults who have Erdheim-Chester disease (ECD) with BRAF V600 mutation.

Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.

The drug was already approved by the FDA to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test.

Now, vemurafenib is the first FDA-approved treatment for ECD.

The FDA previously granted vemurafenib orphan drug and breakthrough therapy designations for this indication, and the supplemental new drug application for vemurafenib in ECD received priority review.

“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”

The application for vemurafenib in ECD was supported by data from the phase 2 VE-BASKET study. Initial results from this study were published in NEJM in August 2015.

VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.

In the 22 patients with ECD, the best overall response rate was 54.5%. Eleven patients experienced a partial response, and 1 patient achieved a complete response.

The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.

The most common adverse events (>50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. The most common grade 3 or higher adverse events (≥10%) were new skin cancers, high blood pressure, rash, and joint pain.

Image from Wikipedia

The US Food and Drug Administration (FDA) has expanded the approved use of vemurafenib (Zelboraf) to include the treatment of adults who have Erdheim-Chester disease (ECD) with BRAF V600 mutation.

Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.

The drug was already approved by the FDA to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test.

Now, vemurafenib is the first FDA-approved treatment for ECD.

The FDA previously granted vemurafenib orphan drug and breakthrough therapy designations for this indication, and the supplemental new drug application for vemurafenib in ECD received priority review.

“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”

The application for vemurafenib in ECD was supported by data from the phase 2 VE-BASKET study. Initial results from this study were published in NEJM in August 2015.

VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.

In the 22 patients with ECD, the best overall response rate was 54.5%. Eleven patients experienced a partial response, and 1 patient achieved a complete response.

The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.

The most common adverse events (>50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. The most common grade 3 or higher adverse events (≥10%) were new skin cancers, high blood pressure, rash, and joint pain.

Image from Wikipedia

The US Food and Drug Administration (FDA) has expanded the approved use of vemurafenib (Zelboraf) to include the treatment of adults who have Erdheim-Chester disease (ECD) with BRAF V600 mutation.

Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.

The drug was already approved by the FDA to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test.

Now, vemurafenib is the first FDA-approved treatment for ECD.

The FDA previously granted vemurafenib orphan drug and breakthrough therapy designations for this indication, and the supplemental new drug application for vemurafenib in ECD received priority review.

“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”

The application for vemurafenib in ECD was supported by data from the phase 2 VE-BASKET study. Initial results from this study were published in NEJM in August 2015.

VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.

In the 22 patients with ECD, the best overall response rate was 54.5%. Eleven patients experienced a partial response, and 1 patient achieved a complete response.

The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.

The most common adverse events (>50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. The most common grade 3 or higher adverse events (≥10%) were new skin cancers, high blood pressure, rash, and joint pain.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to GSK2857916, an anti-B-cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent monomethyl auristatin-F via a non-cleavable linker.

The designation is for GSK2857916 as monotherapy for patients with multiple myeloma (MM) who have failed at least 3 prior lines of therapy, including an anti-CD38 antibody, and who are refractory to a proteasome inhibitor and an immunomodulatory agent.

The designation is based on results from a phase 1, dose-escalation and expansion study in patients with relapsed/refractory MM, irrespective of BCMA expression (NCT02064387).

Data from this ongoing trial are scheduled to be presented December 11 in an oral presentation at the 59th Annual Meeting of the American Society of Hematology (ASH) in Atlanta, Georgia.

GSK2857916 has also received orphan drug designation from the FDA and the European Medicines Agency (EMA) as well as PRIME designation from the EMA.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions. The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Orphan and PRIME designations

The FDA grants orphan designation to therapies intended to treat conditions that affect fewer than 200,000 people in the US. The designation qualifies a drug’s sponsor for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing and 7 years of market exclusivity.

In Europe, sponsors who obtain orphan designation for a potential new medicine benefit from a range of incentives, including protocol assistance, access to the centralized procedure, 10 years of market exclusivity, and fee reductions.

The EMA grants PRIME designation to enhance support for the development of medicines that target an unmet medical need. The designation is based on enhanced interaction between sponsor companies and the EMA to optimize development plans and speed up evaluation so these medicines can reach patients earlier.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to GSK2857916, an anti-B-cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent monomethyl auristatin-F via a non-cleavable linker.

The designation is for GSK2857916 as monotherapy for patients with multiple myeloma (MM) who have failed at least 3 prior lines of therapy, including an anti-CD38 antibody, and who are refractory to a proteasome inhibitor and an immunomodulatory agent.

The designation is based on results from a phase 1, dose-escalation and expansion study in patients with relapsed/refractory MM, irrespective of BCMA expression (NCT02064387).

Data from this ongoing trial are scheduled to be presented December 11 in an oral presentation at the 59th Annual Meeting of the American Society of Hematology (ASH) in Atlanta, Georgia.

GSK2857916 has also received orphan drug designation from the FDA and the European Medicines Agency (EMA) as well as PRIME designation from the EMA.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions. The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Orphan and PRIME designations

The FDA grants orphan designation to therapies intended to treat conditions that affect fewer than 200,000 people in the US. The designation qualifies a drug’s sponsor for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing and 7 years of market exclusivity.

In Europe, sponsors who obtain orphan designation for a potential new medicine benefit from a range of incentives, including protocol assistance, access to the centralized procedure, 10 years of market exclusivity, and fee reductions.

The EMA grants PRIME designation to enhance support for the development of medicines that target an unmet medical need. The designation is based on enhanced interaction between sponsor companies and the EMA to optimize development plans and speed up evaluation so these medicines can reach patients earlier.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to GSK2857916, an anti-B-cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent monomethyl auristatin-F via a non-cleavable linker.

The designation is for GSK2857916 as monotherapy for patients with multiple myeloma (MM) who have failed at least 3 prior lines of therapy, including an anti-CD38 antibody, and who are refractory to a proteasome inhibitor and an immunomodulatory agent.

The designation is based on results from a phase 1, dose-escalation and expansion study in patients with relapsed/refractory MM, irrespective of BCMA expression (NCT02064387).

Data from this ongoing trial are scheduled to be presented December 11 in an oral presentation at the 59th Annual Meeting of the American Society of Hematology (ASH) in Atlanta, Georgia.

GSK2857916 has also received orphan drug designation from the FDA and the European Medicines Agency (EMA) as well as PRIME designation from the EMA.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions. The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Orphan and PRIME designations

The FDA grants orphan designation to therapies intended to treat conditions that affect fewer than 200,000 people in the US. The designation qualifies a drug’s sponsor for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing and 7 years of market exclusivity.

In Europe, sponsors who obtain orphan designation for a potential new medicine benefit from a range of incentives, including protocol assistance, access to the centralized procedure, 10 years of market exclusivity, and fee reductions.

The EMA grants PRIME designation to enhance support for the development of medicines that target an unmet medical need. The designation is based on enhanced interaction between sponsor companies and the EMA to optimize development plans and speed up evaluation so these medicines can reach patients earlier.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo by Esther Dyson

The US Food and Drug Administration (FDA) will now recognize 8 European drug regulatory authorities as capable of conducting inspections of manufacturing facilities that meet FDA requirements.

This move is a step toward successful implementation of the amended Pharmaceutical Annex to the 1998 US-European Union (EU) Mutual Recognition Agreement.

This agreement enables US and EU regulators to utilize each other’s good manufacturing practice (GMP) inspections of pharmaceutical manufacturing facilities.

In June, the European Commission determined that the FDA “has the capability, capacity, and procedures in place to carry out GMP inspections at a level equivalent to the EU.”

Now, the FDA has followed suit. The agency said it will rely on inspections of manufacturing facilities conducted by regulatory authorities located in Austria, Croatia, France, Italy, Malta, Spain, Sweden, and the United Kingdom.

“Beginning November 1, we will take the unprecedented and significant step forward in realizing the key benefits of the Mutual Recognition Agreement with our European counterparts in that we will now rely on the inspectional data obtained by these 8 regulatory agencies,” said Dara Corrigan, the FDA’s acting deputy commissioner for global regulatory operations and policy.

“The progress made so far puts us on track to meet our goal of completing all 28 capability assessments in the EU by July 2019.”

The completion of these capability assessments is intended to reduce duplication of drug inspections and allow regulators to devote more resources to other manufacturing facilities in countries where there may be greater risk.

The FDA believes that, ultimately, the prioritization of such inspections will help identify potential drug quality problems more quickly and prevent poor quality drugs from entering the US market.

“At a time in which medical product manufacturing is truly a global enterprise, there is much to be gained by partnering with regulatory counterparts to reduce duplicative efforts and maximize global resources while realizing the greatest bang for our collective inspectional buck,” said FDA Commissioner Scott Gottlieb, MD.

“By partnering with these countries, we can create greater efficiencies and better fulfill our public health goals, relying on the expertise of our colleagues and refocusing our resources on inspections in higher-risk countries.”

Photo by Esther Dyson

The US Food and Drug Administration (FDA) will now recognize 8 European drug regulatory authorities as capable of conducting inspections of manufacturing facilities that meet FDA requirements.

This move is a step toward successful implementation of the amended Pharmaceutical Annex to the 1998 US-European Union (EU) Mutual Recognition Agreement.

This agreement enables US and EU regulators to utilize each other’s good manufacturing practice (GMP) inspections of pharmaceutical manufacturing facilities.

In June, the European Commission determined that the FDA “has the capability, capacity, and procedures in place to carry out GMP inspections at a level equivalent to the EU.”

Now, the FDA has followed suit. The agency said it will rely on inspections of manufacturing facilities conducted by regulatory authorities located in Austria, Croatia, France, Italy, Malta, Spain, Sweden, and the United Kingdom.

“Beginning November 1, we will take the unprecedented and significant step forward in realizing the key benefits of the Mutual Recognition Agreement with our European counterparts in that we will now rely on the inspectional data obtained by these 8 regulatory agencies,” said Dara Corrigan, the FDA’s acting deputy commissioner for global regulatory operations and policy.

“The progress made so far puts us on track to meet our goal of completing all 28 capability assessments in the EU by July 2019.”

The completion of these capability assessments is intended to reduce duplication of drug inspections and allow regulators to devote more resources to other manufacturing facilities in countries where there may be greater risk.

The FDA believes that, ultimately, the prioritization of such inspections will help identify potential drug quality problems more quickly and prevent poor quality drugs from entering the US market.

“At a time in which medical product manufacturing is truly a global enterprise, there is much to be gained by partnering with regulatory counterparts to reduce duplicative efforts and maximize global resources while realizing the greatest bang for our collective inspectional buck,” said FDA Commissioner Scott Gottlieb, MD.

“By partnering with these countries, we can create greater efficiencies and better fulfill our public health goals, relying on the expertise of our colleagues and refocusing our resources on inspections in higher-risk countries.”

Photo by Esther Dyson

The US Food and Drug Administration (FDA) will now recognize 8 European drug regulatory authorities as capable of conducting inspections of manufacturing facilities that meet FDA requirements.

This move is a step toward successful implementation of the amended Pharmaceutical Annex to the 1998 US-European Union (EU) Mutual Recognition Agreement.

This agreement enables US and EU regulators to utilize each other’s good manufacturing practice (GMP) inspections of pharmaceutical manufacturing facilities.

In June, the European Commission determined that the FDA “has the capability, capacity, and procedures in place to carry out GMP inspections at a level equivalent to the EU.”

Now, the FDA has followed suit. The agency said it will rely on inspections of manufacturing facilities conducted by regulatory authorities located in Austria, Croatia, France, Italy, Malta, Spain, Sweden, and the United Kingdom.

“Beginning November 1, we will take the unprecedented and significant step forward in realizing the key benefits of the Mutual Recognition Agreement with our European counterparts in that we will now rely on the inspectional data obtained by these 8 regulatory agencies,” said Dara Corrigan, the FDA’s acting deputy commissioner for global regulatory operations and policy.

“The progress made so far puts us on track to meet our goal of completing all 28 capability assessments in the EU by July 2019.”

The completion of these capability assessments is intended to reduce duplication of drug inspections and allow regulators to devote more resources to other manufacturing facilities in countries where there may be greater risk.

The FDA believes that, ultimately, the prioritization of such inspections will help identify potential drug quality problems more quickly and prevent poor quality drugs from entering the US market.

“At a time in which medical product manufacturing is truly a global enterprise, there is much to be gained by partnering with regulatory counterparts to reduce duplicative efforts and maximize global resources while realizing the greatest bang for our collective inspectional buck,” said FDA Commissioner Scott Gottlieb, MD.

“By partnering with these countries, we can create greater efficiencies and better fulfill our public health goals, relying on the expertise of our colleagues and refocusing our resources on inspections in higher-risk countries.”

Photo courtesy of Janssen

Health Canada has approved the BTK inhibitor ibrutinib (IMBRUVICA®) for the treatment of patients with steroid-dependent or -refractory chronic graft-versus-host disease (cGVHD).

This is the sixth approval for ibrutinib in Canada.

The drug is approved as monotherapy for patients with previously untreated chronic lymphocytic leukemia (CLL), CLL patients who have received at least 1 prior therapy, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma.

Ibrutinib is also approved for use in combination with bendamustine and rituximab for the treatment of CLL patients who have received at least 1 prior therapy.

Ibrutinib is co-developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics LLC, an AbbVie company. Janssen Inc. markets ibrutinib in Canada.

The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.

The trial included 42 patients with a median age of 56 (range, 19 to 74). The most common underlying malignancies that led to patients’ transplants were acute lymphocytic leukemia, acute myeloid leukemia, and CLL.

At baseline, the patients had persistent cGVHD symptoms despite receiving standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.

The median time since cGVHD diagnosis was 14 months, the median number of prior cGVHD treatments was 2 (range, 1 to 3), and 60% of patients had a Karnofsky performance score of ≤ 80.

Fifty-two percent of patients were receiving ongoing immunosuppressants and systemic corticosteroids at baseline.

Sixty-seven percent of patients responded to treatment with ibrutinib, and 21% had a complete response. In 48% of patients, responses lasted for 5 months or longer. Responses were seen across all organs affected by cGVHD (ie, skin, mouth, gastrointestinal tract, and liver).

The patients’ median steroid dose was reduced over time, from 0.31 mg/kg/day at baseline to 0.14 mg/kg/day at week 48. Five patients were able to completely discontinue corticosteroids while in response.

The most common (≥20%) adverse events (AEs) of all grades were fatigue (57%), bruising (40%), diarrhea (36%), stomatitis (29%), muscle spasms (29%), nausea (26%), hemorrhage (26%), and pneumonia (21%).

Atrial fibrillation (grade 3) occurred in 1 patient (2%). Serious AEs occurred in 52% of patients. The most common serious AEs (2 or more patients) were pneumonia, sepsis (septic shock), cellulitis, headache, and pyrexia.

There were 2 fatal events, a case of pneumonia and a case of pulmonary aspergillosis.

Twenty-four percent of patients discontinued ibrutinib due to AEs. The most common AEs leading to discontinuation were fatigue and pneumonia. AEs leading to dose reductions occurred in 26% of patients.

The recommended dose of ibrutinib for cGVHD is 420 mg (three 140 mg capsules) once daily.

Photo courtesy of Janssen

Health Canada has approved the BTK inhibitor ibrutinib (IMBRUVICA®) for the treatment of patients with steroid-dependent or -refractory chronic graft-versus-host disease (cGVHD).

This is the sixth approval for ibrutinib in Canada.

The drug is approved as monotherapy for patients with previously untreated chronic lymphocytic leukemia (CLL), CLL patients who have received at least 1 prior therapy, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma.

Ibrutinib is also approved for use in combination with bendamustine and rituximab for the treatment of CLL patients who have received at least 1 prior therapy.

Ibrutinib is co-developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics LLC, an AbbVie company. Janssen Inc. markets ibrutinib in Canada.

The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.

The trial included 42 patients with a median age of 56 (range, 19 to 74). The most common underlying malignancies that led to patients’ transplants were acute lymphocytic leukemia, acute myeloid leukemia, and CLL.

At baseline, the patients had persistent cGVHD symptoms despite receiving standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.

The median time since cGVHD diagnosis was 14 months, the median number of prior cGVHD treatments was 2 (range, 1 to 3), and 60% of patients had a Karnofsky performance score of ≤ 80.

Fifty-two percent of patients were receiving ongoing immunosuppressants and systemic corticosteroids at baseline.

Sixty-seven percent of patients responded to treatment with ibrutinib, and 21% had a complete response. In 48% of patients, responses lasted for 5 months or longer. Responses were seen across all organs affected by cGVHD (ie, skin, mouth, gastrointestinal tract, and liver).

The patients’ median steroid dose was reduced over time, from 0.31 mg/kg/day at baseline to 0.14 mg/kg/day at week 48. Five patients were able to completely discontinue corticosteroids while in response.

The most common (≥20%) adverse events (AEs) of all grades were fatigue (57%), bruising (40%), diarrhea (36%), stomatitis (29%), muscle spasms (29%), nausea (26%), hemorrhage (26%), and pneumonia (21%).

Atrial fibrillation (grade 3) occurred in 1 patient (2%). Serious AEs occurred in 52% of patients. The most common serious AEs (2 or more patients) were pneumonia, sepsis (septic shock), cellulitis, headache, and pyrexia.

There were 2 fatal events, a case of pneumonia and a case of pulmonary aspergillosis.

Twenty-four percent of patients discontinued ibrutinib due to AEs. The most common AEs leading to discontinuation were fatigue and pneumonia. AEs leading to dose reductions occurred in 26% of patients.

The recommended dose of ibrutinib for cGVHD is 420 mg (three 140 mg capsules) once daily.

Photo courtesy of Janssen

Health Canada has approved the BTK inhibitor ibrutinib (IMBRUVICA®) for the treatment of patients with steroid-dependent or -refractory chronic graft-versus-host disease (cGVHD).

This is the sixth approval for ibrutinib in Canada.

The drug is approved as monotherapy for patients with previously untreated chronic lymphocytic leukemia (CLL), CLL patients who have received at least 1 prior therapy, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma.

Ibrutinib is also approved for use in combination with bendamustine and rituximab for the treatment of CLL patients who have received at least 1 prior therapy.

Ibrutinib is co-developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics LLC, an AbbVie company. Janssen Inc. markets ibrutinib in Canada.

The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.

The trial included 42 patients with a median age of 56 (range, 19 to 74). The most common underlying malignancies that led to patients’ transplants were acute lymphocytic leukemia, acute myeloid leukemia, and CLL.

At baseline, the patients had persistent cGVHD symptoms despite receiving standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.

The median time since cGVHD diagnosis was 14 months, the median number of prior cGVHD treatments was 2 (range, 1 to 3), and 60% of patients had a Karnofsky performance score of ≤ 80.

Fifty-two percent of patients were receiving ongoing immunosuppressants and systemic corticosteroids at baseline.

Sixty-seven percent of patients responded to treatment with ibrutinib, and 21% had a complete response. In 48% of patients, responses lasted for 5 months or longer. Responses were seen across all organs affected by cGVHD (ie, skin, mouth, gastrointestinal tract, and liver).

The patients’ median steroid dose was reduced over time, from 0.31 mg/kg/day at baseline to 0.14 mg/kg/day at week 48. Five patients were able to completely discontinue corticosteroids while in response.

The most common (≥20%) adverse events (AEs) of all grades were fatigue (57%), bruising (40%), diarrhea (36%), stomatitis (29%), muscle spasms (29%), nausea (26%), hemorrhage (26%), and pneumonia (21%).

Atrial fibrillation (grade 3) occurred in 1 patient (2%). Serious AEs occurred in 52% of patients. The most common serious AEs (2 or more patients) were pneumonia, sepsis (septic shock), cellulitis, headache, and pyrexia.

There were 2 fatal events, a case of pneumonia and a case of pulmonary aspergillosis.

Twenty-four percent of patients discontinued ibrutinib due to AEs. The most common AEs leading to discontinuation were fatigue and pneumonia. AEs leading to dose reductions occurred in 26% of patients.

The recommended dose of ibrutinib for cGVHD is 420 mg (three 140 mg capsules) once daily.

Rivaroxaban

The US Food and Drug Administration (FDA) has approved use of a 10 mg once-daily dose of the factor Xa inhibitor rivaroxaban (XARELTO®).

This dose is now approved to reduce the risk of recurrent venous thromboembolism (VTE) in patients who have received at least 6 months of standard anticoagulant therapy.

With this approval, the rivaroxaban prescribing information provides instructions for physicians to begin treatment with rivaroxaban at 15 mg, dosed twice daily, for the first 21 days after a VTE occurrence.

On day 22 through at least day 180, the dose decreases to 20 mg once daily. After at least 180 days (6 months), physicians can prescribe 10 mg once daily in patients at continued risk for deep vein thrombosis and/or pulmonary embolism.

The FDA’s approval of a 10 mg once-daily dose of rivaroxaban follows a priority review designation from the FDA and is based on data from the EINSTEIN CHOICE study.

Results from EINSTEIN CHOICE were presented at the American College of Cardiology’s 66th Annual Scientific Session and published in NEJM in March.

Patients enrolled in this phase 3 study had confirmed VTE and were treated initially with standard anticoagulant therapy for 6 to 12 months.

During the study, 3365 patients received rivaroxaban at 10 mg, rivaroxaban at 20 mg, or aspirin at 100 mg once daily for up to 12 months of extended treatment.

Both rivaroxaban doses were superior to aspirin in preventing fatal or non-fatal recurrent VTE, the study’s primary efficacy endpoint.

The rate of recurrent VTE was 1.2% in the 10 mg rivaroxaban arm (hazard ratio [HR]=0.26; 95% CI, 0.14 to 0.47; P<0.001), 1.5% in the 20 mg rivaroxaban arm (HR=0.34; 95% CI, 0.20 to 0.59; P<0.001), and 4.4% in the aspirin arm. Fatal VTE occurred in 0%, 0.2%, and 0.2% of patients, respectively.

The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.

The rate of major bleeding was 0.4% for the 10 mg rivaroxaban arm (HR=1.64; 95% CI, 0.39 to 6.84; P=0.50), 0.5% for the 20 mg rivaroxaban arm (HR=2.01; 95% CI, 0.50 to 8.04; P=0.32), and 0.3% for the aspirin arm.

Rivaroxaban

The US Food and Drug Administration (FDA) has approved use of a 10 mg once-daily dose of the factor Xa inhibitor rivaroxaban (XARELTO®).

This dose is now approved to reduce the risk of recurrent venous thromboembolism (VTE) in patients who have received at least 6 months of standard anticoagulant therapy.

With this approval, the rivaroxaban prescribing information provides instructions for physicians to begin treatment with rivaroxaban at 15 mg, dosed twice daily, for the first 21 days after a VTE occurrence.

On day 22 through at least day 180, the dose decreases to 20 mg once daily. After at least 180 days (6 months), physicians can prescribe 10 mg once daily in patients at continued risk for deep vein thrombosis and/or pulmonary embolism.

The FDA’s approval of a 10 mg once-daily dose of rivaroxaban follows a priority review designation from the FDA and is based on data from the EINSTEIN CHOICE study.

Results from EINSTEIN CHOICE were presented at the American College of Cardiology’s 66th Annual Scientific Session and published in NEJM in March.

Patients enrolled in this phase 3 study had confirmed VTE and were treated initially with standard anticoagulant therapy for 6 to 12 months.

During the study, 3365 patients received rivaroxaban at 10 mg, rivaroxaban at 20 mg, or aspirin at 100 mg once daily for up to 12 months of extended treatment.

Both rivaroxaban doses were superior to aspirin in preventing fatal or non-fatal recurrent VTE, the study’s primary efficacy endpoint.

The rate of recurrent VTE was 1.2% in the 10 mg rivaroxaban arm (hazard ratio [HR]=0.26; 95% CI, 0.14 to 0.47; P<0.001), 1.5% in the 20 mg rivaroxaban arm (HR=0.34; 95% CI, 0.20 to 0.59; P<0.001), and 4.4% in the aspirin arm. Fatal VTE occurred in 0%, 0.2%, and 0.2% of patients, respectively.

The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.

The rate of major bleeding was 0.4% for the 10 mg rivaroxaban arm (HR=1.64; 95% CI, 0.39 to 6.84; P=0.50), 0.5% for the 20 mg rivaroxaban arm (HR=2.01; 95% CI, 0.50 to 8.04; P=0.32), and 0.3% for the aspirin arm.

Rivaroxaban

The US Food and Drug Administration (FDA) has approved use of a 10 mg once-daily dose of the factor Xa inhibitor rivaroxaban (XARELTO®).

This dose is now approved to reduce the risk of recurrent venous thromboembolism (VTE) in patients who have received at least 6 months of standard anticoagulant therapy.

With this approval, the rivaroxaban prescribing information provides instructions for physicians to begin treatment with rivaroxaban at 15 mg, dosed twice daily, for the first 21 days after a VTE occurrence.

On day 22 through at least day 180, the dose decreases to 20 mg once daily. After at least 180 days (6 months), physicians can prescribe 10 mg once daily in patients at continued risk for deep vein thrombosis and/or pulmonary embolism.

The FDA’s approval of a 10 mg once-daily dose of rivaroxaban follows a priority review designation from the FDA and is based on data from the EINSTEIN CHOICE study.

Results from EINSTEIN CHOICE were presented at the American College of Cardiology’s 66th Annual Scientific Session and published in NEJM in March.

Patients enrolled in this phase 3 study had confirmed VTE and were treated initially with standard anticoagulant therapy for 6 to 12 months.

During the study, 3365 patients received rivaroxaban at 10 mg, rivaroxaban at 20 mg, or aspirin at 100 mg once daily for up to 12 months of extended treatment.

Both rivaroxaban doses were superior to aspirin in preventing fatal or non-fatal recurrent VTE, the study’s primary efficacy endpoint.

The rate of recurrent VTE was 1.2% in the 10 mg rivaroxaban arm (hazard ratio [HR]=0.26; 95% CI, 0.14 to 0.47; P<0.001), 1.5% in the 20 mg rivaroxaban arm (HR=0.34; 95% CI, 0.20 to 0.59; P<0.001), and 4.4% in the aspirin arm. Fatal VTE occurred in 0%, 0.2%, and 0.2% of patients, respectively.

The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.

The rate of major bleeding was 0.4% for the 10 mg rivaroxaban arm (HR=1.64; 95% CI, 0.39 to 6.84; P=0.50), 0.5% for the 20 mg rivaroxaban arm (HR=2.01; 95% CI, 0.50 to 8.04; P=0.32), and 0.3% for the aspirin arm.

Photo from TESARO

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of rolapitant (VARUBI®) for the same indication as the oral formulation.

This means IV rolapitant is now FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy in adults with cancer.

TESARO Inc., makers of rolapitant, said the US commercial launch of IV rolapitant is planned for November.

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV).

IV rolapitant features a ready-to-use, single-dose vial for administration. It does not require refrigerated storage or mixing.

The recommended dose of IV rolapitant is 166.5 mg, administered over 30 minutes. The drug is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information for IV rolapitant is available at www.varubirx.com.

Bioequivalence trial

Results from a bioequivalence trial suggest the IV and oral formulations of rolapitant are comparable.

The study was conducted in healthy volunteers. Subjects were randomized to receive a single dose of IV rolapitant at 166.5 mg administered over 30 minutes (n=61) or oral rolapitant at 180 mg (n=62).

The primary endpoint was bioequivalence, and the 166.5 mg IV infusion of rolapitant met bioequivalence criteria.

Researchers said the safety profile of IV rolapitant was largely consistent with that of oral rolapitant, although infusion-site reactions were observed with the IV formulation. These included the sensation of warmth, abdominal pain, dizziness, and paresthesia.

These results were recently published in The Journal of Clinical Pharmacology.

Oral rolapitant trials

Two phase 3 trials showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after highly emetogenic chemotherapy.

Results from these trials (NCT01499849 and NCT01500213) were published in a single article in The Lancet Oncology.

A third phase 3 trial showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after moderately emetogenic chemotherapy.

Results from this trial (NCT01500226) were also published in The Lancet Oncology.

Photo from TESARO

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of rolapitant (VARUBI®) for the same indication as the oral formulation.

This means IV rolapitant is now FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy in adults with cancer.

TESARO Inc., makers of rolapitant, said the US commercial launch of IV rolapitant is planned for November.

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV).

IV rolapitant features a ready-to-use, single-dose vial for administration. It does not require refrigerated storage or mixing.

The recommended dose of IV rolapitant is 166.5 mg, administered over 30 minutes. The drug is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information for IV rolapitant is available at www.varubirx.com.

Bioequivalence trial

Results from a bioequivalence trial suggest the IV and oral formulations of rolapitant are comparable.

The study was conducted in healthy volunteers. Subjects were randomized to receive a single dose of IV rolapitant at 166.5 mg administered over 30 minutes (n=61) or oral rolapitant at 180 mg (n=62).

The primary endpoint was bioequivalence, and the 166.5 mg IV infusion of rolapitant met bioequivalence criteria.

Researchers said the safety profile of IV rolapitant was largely consistent with that of oral rolapitant, although infusion-site reactions were observed with the IV formulation. These included the sensation of warmth, abdominal pain, dizziness, and paresthesia.

These results were recently published in The Journal of Clinical Pharmacology.

Oral rolapitant trials

Two phase 3 trials showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after highly emetogenic chemotherapy.

Results from these trials (NCT01499849 and NCT01500213) were published in a single article in The Lancet Oncology.

A third phase 3 trial showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after moderately emetogenic chemotherapy.

Results from this trial (NCT01500226) were also published in The Lancet Oncology.

Photo from TESARO

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of rolapitant (VARUBI®) for the same indication as the oral formulation.

This means IV rolapitant is now FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy in adults with cancer.

TESARO Inc., makers of rolapitant, said the US commercial launch of IV rolapitant is planned for November.

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV).

IV rolapitant features a ready-to-use, single-dose vial for administration. It does not require refrigerated storage or mixing.

The recommended dose of IV rolapitant is 166.5 mg, administered over 30 minutes. The drug is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information for IV rolapitant is available at www.varubirx.com.

Bioequivalence trial

Results from a bioequivalence trial suggest the IV and oral formulations of rolapitant are comparable.

The study was conducted in healthy volunteers. Subjects were randomized to receive a single dose of IV rolapitant at 166.5 mg administered over 30 minutes (n=61) or oral rolapitant at 180 mg (n=62).

The primary endpoint was bioequivalence, and the 166.5 mg IV infusion of rolapitant met bioequivalence criteria.

Researchers said the safety profile of IV rolapitant was largely consistent with that of oral rolapitant, although infusion-site reactions were observed with the IV formulation. These included the sensation of warmth, abdominal pain, dizziness, and paresthesia.

These results were recently published in The Journal of Clinical Pharmacology.

Oral rolapitant trials

Two phase 3 trials showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after highly emetogenic chemotherapy.

Results from these trials (NCT01499849 and NCT01500213) were published in a single article in The Lancet Oncology.

A third phase 3 trial showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after moderately emetogenic chemotherapy.

Results from this trial (NCT01500226) were also published in The Lancet Oncology.

Photo courtesy of Biogen

The Saudi Food and Drug Authority has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B in the Kingdom of Saudi Arabia.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for on-demand treatment and prophylaxis in hemophilia B patients of all ages.

Eftrenonacog alfa is engineered by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is approved to treat hemophilia B in the European Union, Iceland, Liechtenstein, Kuwait, Norway, and Switzerland (where it is marketed by Sobi). The product is also approved in the US, Canada, Japan, Australia, New Zealand, and other countries (where it is marketed by Bioverativ).

The approvals of eftrenonacog alfa are based on results from a pair of phase 3 trials—the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 males with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

• Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
• Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
• On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
• Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated males younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. There were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Photo courtesy of Biogen

The Saudi Food and Drug Authority has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B in the Kingdom of Saudi Arabia.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for on-demand treatment and prophylaxis in hemophilia B patients of all ages.

Eftrenonacog alfa is engineered by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is approved to treat hemophilia B in the European Union, Iceland, Liechtenstein, Kuwait, Norway, and Switzerland (where it is marketed by Sobi). The product is also approved in the US, Canada, Japan, Australia, New Zealand, and other countries (where it is marketed by Bioverativ).

The approvals of eftrenonacog alfa are based on results from a pair of phase 3 trials—the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 males with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

• Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
• Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
• On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
• Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated males younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. There were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Photo courtesy of Biogen

The Saudi Food and Drug Authority has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B in the Kingdom of Saudi Arabia.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for on-demand treatment and prophylaxis in hemophilia B patients of all ages.

Eftrenonacog alfa is engineered by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is approved to treat hemophilia B in the European Union, Iceland, Liechtenstein, Kuwait, Norway, and Switzerland (where it is marketed by Sobi). The product is also approved in the US, Canada, Japan, Australia, New Zealand, and other countries (where it is marketed by Bioverativ).

The approvals of eftrenonacog alfa are based on results from a pair of phase 3 trials—the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 males with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

• Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
• Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
• On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
• Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated males younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. There were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.